Recent Submissions

  • Influence of Porphyromonas gingivalis on Anti-Apoptotic/Autophagic Signaling Pathways in Human Dendritic Cells

    Meghil, Mohamed; Tawfik, Omnia; Elashirty, Mahmoud; Rajendran, Mythilypriya; Arce, Roger; Schoenlein, Patricia V.; Cutler, Christopher; Department of Oral Biology & Diagnostic Sciences, Department of Periodontics, Department of Cellular Biology and Anatomy (Augusta University, 2019)
    The purpose of this study was to investigate the molecular mechanisims of P. gingivalis-mediated disruption of homeostatic apoptosis and autophagy in DCs.

    Vick, Sarah; Department of Biological Sciences; Department of Cellular Biology and Anatomy; Lu, Xiaowen; Watsky, Mitchell; Augusta University (2019-02-13)
    It is estimated that 41.6% of the US population suffers from vitamin D deficiency, with Blacks (82.1%) and Hispanics (69.2%) at even greater risk�Vitamin D deficiency can be caused by a variety of sources and given the wide range of causes, it is important to understand what measures this population might take to proactively prevent greater harm, or to reverse harm that might have already occurred. This project is designed to test the general hypothesis that Vitamin D deficiency exacerbates preexisting primary corneal pathologies. Previous research has established that the corneal epithelium in diabetic mice heals at a faster rate than the epithelium in diabetic vitamin D receptor (VDR) knockout (KO) mice. It is known that within diabetic mice, the corneal nerve density is decreased. However, it is unknown how VDR KO mice or vitamin D deficient with diabetes will affect corneal nerve density. In order to identify variabilities within the nerves that indicate slow wound healing, the mouse corneas will be collected, stained for confocal microscope observation, and analyzed through image processing to determine nerve density.
  • Salubrinal Mediated Fetal Hemoglobin Induction Through The PERK-eIF2α-ATF4 Signaling Pathway

    Lopez, Nicole; Department of Cellular Biology and Anatomy (2016-03)
    Sickle cell disease (SCD) is an inherited disorder caused by a point mutation in the β-globin gene affecting ~100,000 people in the United States. These individuals suffer from hemolytic anemia, pain, and progressive organ damage. The best therapeutic intervention in SCD is fetal hemoglobin (HbF) induction by pharmacologic agents, however, Hydroxyurea is the only FDA-approved drug with proven efficacy. The goal of this project is to discover drugs that induce HbF by novel mechanisms for SCD treatment. Salubrinal (SAL), a selective inhibitor of eukaryotic initiation factor 2α (eIF2α), was shown to increase HbF levels by enhancing γ-globin mRNA translation. These findings lead us to test the hypothesis that SAL activates the PERK-eIF2α-ATF4 stress response, as a mechanism of HbF induction in erythroid progenitors. Studies were conducted in K562 and erythroid progenitor generated from CD34+ stem cells treated with SAL (5, 12, and 18µM) for 48hr. RT-qPCR and western blot were used to measure γ-globin mRNA and HbF protein levels respectively. Preliminary data revealed a dose-dependent increase for HbF levels in K562 and erythroid progenitors treated with SAL. Flow cytometry showed an increase in the number of cells producing HbF (%F-cells). Furthermore, eIF2α and ATF4 levels were increased by SAL in K562 cells. These findings suggest SAL mediates HbF induction through eIF2α/ATF-4 signaling; future studies using the preclinical sickle cell mouse model will be investigated.
  • Deletion of the Mammalian Homolog of Yeast Vacuolar Protein Sorting 34 Inhibits Compensatory Nephron Hypertrophy

    Liu, Ting; Department of Cellular Biology and Anatomy (2016-03)
    Reduction of functioning nephrons stimulates all components of the remaining nephrons, particularly the proximal tubule, to undergo compensatory nephron hypertrophy (CNH). Recent studies in our lab revealed activation of the mammalian homolog of yeast vacuolar protein sorting 34 (mVPS34) in the remaining kidney within 30 min in response to uninephrectomy (UNX). Interestingly, mVPS34 has been reported to be an upstream mediator of mTORC1 activation in cultured cells. However, whether mVPS34 activation is essential in mediating mTORC1 signaling to CNH in vivo remains unknown. We crossed mVPS34flox/flox mice with SG.Cre mice expressing tamoxifen-inducible Cre recombinase mainly in the S1 and S2 segments of the proximal tubule and generated proximal tubule-specific mVPS34 knockout (mVPS34ptKO) mice. The body weight and kidney/body weight ratio (K/Bwt) of mVPS34ptKO mice were similar to those of wild type control (mVPS34Ctrl) littermates. 8-week-old mVPS34Ctrl and mVPS34ptKO mice were uninephrectomized. UNX-induced CNH in mVPS34ptKO mice was blocked by 40-55%, as indicated by inhibition of increases in K/Bwt ratio compared to that of mVPS34Ctrl mice (15.81±2.82 vs. 33.15±1.97%; p<0.001, n=7-9). There was no change in BUN levels in mVPS34ptKO and mVPS34ctrl mice with or without UNX. This study provided the first genetic evidence that mVPS34 mediates 40-55% of CNH. Further studies will determine the interactions between mVPS34 activation and mTORC1 signaling in regulating CNH.